Lack of association of Toll-like receptor 9 polymorphisms with susceptibility to systemic lupus erythematosus in an Asian population: a meta-analysis

The association of Toll-like receptor 9 (TLR9) gene polymorphisms with systemic lupus erythematosus (SLE) risk remains controversial and ambiguous. To more precisely estimate the relationship between TLR9 gene polymorphisms and the susceptibility to SLE, a meta-analysis was performed. A total of seven independent studies were involved in this analysis. Meta-analysis was performed for three TLR9 gene polymorphisms (rs187084, rs352139, and rs352140). We have compared allele or genotype frequencies of the polymorphisms in SLE patients and controls. When available studies were pooled into the meta-analysis, there was no evidence showing a significant association between rs187084 and SLE risk in an Asian population (for C vs. T: OR?=?0.81, P?=?0.117; for CC vs. TT: OR?=?0.71, P?=?0.158; for CT vs. TT: OR?=?0.86, P?=?0.085; for CC?+?CT vs. TT: OR?=?0.78, P?=?0.093; for CC vs. CT?+?TT: OR?=?0.81, P?=?0.285). Similar results were found between rs352139 and SLE. No significant association was detected in any genetic model in the Asian population either (for G vs. A: OR?=?1.11, P?=?0.095; for GG vs. AA: OR?=?1.32, P?=?0.238; for GA vs. AA: OR?=?1.17, P?=?0.084; for GG?+?GA vs. AA: OR?=?1.17, P?=?0.073; for GG vs. GA?+?AA: OR?=?1.17, P?=?0.404). We found no association between TLR9 gene rs352140 polymorphism and SLE in the Asian population (for A vs. G: OR?=?1.02, P?=?0.728). In conclusion, there is still not enough evidence to indicate an association between TLR9 gene rs187084, rs352139, and rs352140 polymorphisms and the development of SLE in the Asian population.     

TLR9 polymorphisms and systemic lupus erythematosus risk: an update meta-analysis study

It has been reported that the Toll-like receptor 9 (TLR9) gene polymorphisms may be associated with systemic lupus erythematosus (SLE) risk. However, some studies yielded conflicting results. Therefore, a comprehensive meta-analysis was performed to assess the precise association between TLR9 polymorphisms and SLE susceptibility. We performed a systematic search in PubMed, Embase (Ovid), China National Knowledge Internet, and Wanfang databases up to July 15, 2015. Odds ratio (OR) and 95 % confidence interval (CI) were used to pool the effect size. Statistical analyses were performed with STATA 11.0 software. In total, 21 studies from nineteen articles with 10,273 subjects were included in this meta-analysis. The overall results suggested that there was a statistically significant association between TLR9 rs187084 polymorphism and SLE risk observed in recessive model (TT vs. TC + CC: OR 1.17, 95 % CI 1.05–1.30, P = 0.005), codominant model (TT vs. CC: OR 1.22, 95 % CI 1.03–1.43, P = 0.019), and allele model (T vs. C: OR 1.15, 95 % CI 1.02–1.30, P = 0.020) in Asians. However, we found that there may be no significant association between the other three TLR9 polymorphisms and SLE risk in either Asians or non-Asians. In conclusion, the meta-analysis results suggested that TLR9 rs187084 polymorphism may increase the risk of SLE in Asians. However, no significant association between TLR9 SNPs (rs352139, rs352140, and rs5743836) and SLE risk was identified.     

Association of toll-like receptor 9 gene polymorphism in Chinese patients with systemic lupus erythematosus in Taiwan

The purpose of this study was to determine whether toll-like receptor 9 (TLR9) gene polymorphisms were markers of susceptibility to or severity of systemic lupus erythematosus (SLE) in Taiwanese patients. The study included 211 healthy individuals and 167 Chinese patients with SLE. Polymorphisms of TLR9 [rs2066807 and rs187084 (?1486 T/C)] were typed from genomic DNA. The genotypes, allelic frequencies, and carriage rates were compared between patients with SLE and control subjects. The relationship between allelic frequencies and clinical manifestations of 167 patients with SLE was evaluated. There was no statistically significant difference in TLR9 (rs2066807) gene polymorphism, allelic frequency, and carriage rate between the SLE and control groups. However, for the genotype of TLR9 ?1486 T/C (rs187084) polymorphism, there was a statistically significant difference between the SLE and the control groups (P?<?0.001, χ²?=?15.9). Moreover, there was a significant association between the two groups in allelic frequency and carriage rate of the T allele (P?<?0.001, χ²?=?18.5 and P?<?0.01, χ²?=?8.06, respectively). We did not detect any association between the TLR9 genotype and the clinical or laboratory profiles in patients with SLE. The results suggest that the TLR9 ?1486 T/C (rs187084), but not TLR9 (rs2066807), polymorphism is related to SLE in Taiwanese patients.     

Toll-Like Receptor (TLR)-9 rs352140 Polymorphism is an Immunopathology Protective Factor in Parkinson's Disease in the Northern Iranian Population

Background: Neuroinflammation and immunopathology in Parkinson's disease (PD) are believed to be associated with genetic and environmental factors. Objective: We conducted the current study to evaluate the Toll-like receptors (TLR4 and TLR9) genes polymorphism in patients with Parkinson's disease in northern Iran. Methods: We extracted DNA from peripheral blood samples of 100 sporadic cases of Parkinson's disease and 100 healthy-matched controls with the mean age of 69.98 and 71.94 years, respectively. Subsequently, single-nucleotide polymorphisms (SNPs) of TLR4 and TLR9 were genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results were confirmed employing Sanger sequencing. For the analysis of our data, we used SNPStats and SPSS 22 software. Results: Our findings indicated that the allele distribution for rs352140 of TLR9 gene was significantly different in the PD group compared with the healthy controls (p=0.02). Moreover, rs352140 T allele was observed to be correlated with PD reduced risk (TT + TC vs. CC). The dominant rs352140 model was approved as the most acceptable inheritance model for fitting the data (OR 0.41, 95% CI 0.23-0.75, p=0.0031). Additionally, haplotype analysis revealed a significant correlation between TLR9 polymorphisms and Parkinson's disease. Conclusion: The results of this study indicated that rs352140T of TLR9 gene was a protective factor in Parkinson's disease. Furthermore, this SNP could be regarded as a prognostic factor. However, this conclusion should be confirmed by further investigations.     

Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis

Abstract

Introduction To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) risk, we surveyed studies on the association of the TNFSF4 rs2205960, rs1234315, rs844644, and rs844648 polymorphisms with SLE.

Methods A literature-based search was conducted to identify all relevant studies. A total of eight independent studies were identified and subsequently reviewed in the meta-analysis.

Results The meta-analysis showed an association between the TNFSF4 rs2205960 polymorphism and SLE in all subjects [ odds ratio (OR) 1.327, 95 % confidence interval (CI) 1.227–1.436, P < 0.001]. In a subgroup analysis by ethnicity, a significantly increased risk for SLE was associated with TNFSF4 rs2205960 T allele among patients of European (OR 1.254, 95 % CI 1.185–1.328, P < 0.001) and Asian ethnicity (OR 1.425, 95 % CI 1.352–1.501, P < 0.001). The meta-analysis of the rs1234315 polymorphism revealed no association between SLE and the rs1234315 T allele in all subjects (OR 1.167, 95 % CI 0.874–1.558, P = 0.296), but the results of the subgroup analysis revealed significant association in subjects of Asian ethnicity (OR 1.386, 95 % CI 1.318–1.458, P < 0.001). No association was found between the rs844644 and rs844648 polymorphisms and SLE.

Conclusion The results of our meta-analysis suggest that the TNFSF4 rs2205960 polymorphism may confer susceptibility to SLE in different populations and that the TNFSF4 rs1234315 polymorphism is associated with susceptibility to SLE in Asians.     

IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide polymorphisms

Objective: There has been significant interest in the association between asthma and the polymorphisms of IL-17A and IL-17F for a period of time. This work aims to present a clearer relationship between asthma and the polymorphisms of IL-17A and IL-17F. Method: Searches were performed in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between polymorphisms of IL-17A and IL-17F and asthma. Results: Nine studies comprising 3650 asthmatics and 3370 controls were included in this meta-analysis for all single nucleotide polymorphisms (SNPs) (2–6 per SNP). Our study examined the polymorphisms of IL-17F rs1889570 (C/T) (CC versus TT: OR?=?0.55, 95%CI?=?0.41–0.75; CT versus TT: OR?=?0.54, 95%CI?=?0.40–0.72; CC/CT versus TT: OR?=?0.55, 95%CI?=?0.42–0.72; CC versus CT/TT, OR?=?1.83, 95%CI?=?1.39–2.41), IL-17A rs4711998(A/G) (AA/AG versus GG: OR?=?0.67, 95%CI?=?0.46–0.98), and IL-17A rs3819024(A/G) (AA versus GG: OR?=?1.77, 95%CI?=?1.39–2.25) and found they were significantly related to the risk of asthma. Conclusion: Our systematic review showed that IL-17F rs1889570(C/T), IL-17A rs4711998(A/G) and IL-17A rs3819024(A/G) may be potential risk factors for asthma susceptibility.     

TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and can affect several organs and systems. It is characterized by high production of autoantibodies against nuclear compounds. TLR7/8/9 are responsible for nucleic acid recognition and they trigger proinflammatory responses through activation of NK-kappaB and Type I IFN production, making a bridge between the innate and the adaptative immune systems. We analyzed the frequency of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and rs352140 in 370 patients with SLE and 415 healthy controls from southern Brazil. All analyses were conducted with regard to gender and ethnicity. Genotypic and allelic frequencies were different for TLR7 rs179008 (0.253 vs. 0.163, p = 0.020 and p = 0.003, OR for T allele: 1.74 CI 95% 1.12-2.70) and TLR9 rs5743836 (0.174 vs. 0.112, p = 0.045 and p = 0.017, OR for C allele: 1.59, CI 95% 0.99-2.57) between European-derived female groups. A higher frequency was observed for the presence of Anti-SSa/Ro for TRL9 rs5743836 C allele carriers (0.228 vs 0.126, Bonferroni corrected p = 0.06). No statistical differences were found for TLR9 haplotypic analyses. We suggest that TLR7 rs179008 and TLR9 rs5743836 can be considered SLE susceptibility factors for women of European descent in our population.     

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086–7.090, p?=?0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727–6.661, p?=?0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379–1.472, p?=?0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544–1.956, p?=?0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.     

Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73–0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66–0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55–0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00–2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72–1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68–1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86–2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70–1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.     

Association of interleukin-10 polymorphisms with risk of irritable bowel syndrome:A meta-analysis

AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.     

The PSCA polymorphisms derived from genome-wide association study are associated with risk of gastric cancer: a meta-analysis

Purpose

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-aa protein related to the cell-proliferation inhibition and/or cell-death induction activity. Many studies had reported the role of PSCA rs2294008 C?>?T and rs2976392 G?>?A polymorphisms on gastric cancer risk.

Methods

To investigate a more precise estimation of the relationships, we performed a meta-analysis on 9 case–control studies included 10,746 cases and 9,158 controls. Odds ratios (ORs) and 95?% confidence intervals (CIs) were used to assess the strength of the association.

Results

For PSCA rs2294008 C?>?T polymorphism, there was a significantly increased risk of gastric cancer in all genetic models (TT/TC vs. CC: OR?=?1.61, 95?% CI?=?1.35–1.91; TT vs. TC/CC: OR?=?1.33, 95?% CI?=?1.24–1.42). Similar results were also observed for PSCA rs2976392 G?>?A polymorphism (AA/AG vs. GG: OR?=?1.69, 95?% CI?=?1.24–2.31; AA vs. AG/GG: OR?=?1.36, 95?% CI?=?1.24–1.50). In the stratified analysis by ethnicity of rs2294008, an increased gastric cancer risk was found in both Asians (TT vs. TC/CC: OR?=?1.31, 95?% CI?=?1.22–1.42) and Europeans (TT/TC vs. CC: OR?=?1.42, 95?% CI?=?1.18–1.71). Furthermore, when stratified by clinicopathologic characteristics of tumor location and histology, a higher risk on non-cardia compared with cardia gastric cancer (TT vs. TC/CC: OR?=?1.43, 95?% CI?=?1.12–1.83) as same as diffused compared with intestinal gastric cancer (TT vs. TC/CC: OR?=?1.29, 95?% CI?=?1.13–1.49) was observed.

Conclusion

These findings supported that PSCA rs2294008 C?>?T and rs2976392 G?>?A polymorphisms may contribute to the susceptibility to gastric cancer, particular in non-cardia or diffused gastric cancer.     

IL28B polymorphisms predict response to therapy among chronic hepatitis C patients with HCV genotype 4

Summary. Genetic polymorphisms near IL28B are associated with spontaneous and treatment‐induced clearance of hepatitis C virus (HCV). Our objective was to assess the predictive value of IL28B polymorphisms in the treatment of chronic hepatitis C of patients with HCV genotypes 4, for which data are currently limited. We analysed the association of IL28B polymorphisms with the virological response to treatment among 182 naïve chronic hepatitis C patients with HCV genotype 4, all from Syria. Associations of alleles with the response patterns were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. Sustained virological response (SVR) was achieved in 26% of rs8099917 TG/GG carriers compared with 60% of TT carriers (P < 0.0001) and 35% of rs12979860 CT/TT carriers compared with 62% of CC carriers (P = 0.0011). By multivariate analysis, the association between rs8099917 and SVR remained significant (OR = 0.19, 95% CI 0.07–0.50, for TG/GG vs TT, P = 0.0007), with the only significant covariate being advanced fibrosis (OR = 0.13, 95% CI 0.04–0.37, P = 0.0002). In conclusion, IL28B polymorphisms are the strongest predictors of response to therapy among chronic hepatitis C patients with HCV genotype 4.     

Lysosomal acid lipase gene single nucleotide polymorphism and pulmonary tuberculosis susceptibility

BackgroundThe factors that predispose to pulmonary tuberculosis (PTB) are not fully understood, However. Gene polymorphisms have been associated with PTB development.ObjectivesIn this study, we investigated the relationship between LIPA gene polymorphisms and a predisposition to pulmonary tuberculosis caused by Mycobacterium tuberculosis.MethodsA total of 202 cases of PTB and 218 healthy controls (HCS) were included in this study. Analyses were done under allelic, homozygous, and heterozygous, dominant, recessive models, and were used to calculate values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk. Genotyping was conducted using the real time polymerase chain reaction with high resolution melting curve analysis.ResultsWhen comparing PTB patients with healthy controls (HCS), significant associations with disease development were observed for both SNPs rs1051338 and rs7922269. Analysis was done based on models of genetic inheritance in man that is co-dominant, recessive and dominant models. Rs1051338, the heterozygous (AC vs. AA) P: 0.001, OR: 1.998, 95% CI: 1.312–3.042 and homozygous (CC vs. AA) P: < 0.001, OR: 4.078, 95% CI: 2.134–7.796 Co-dominant associated with increased risk for the disease. Under recessive (CC vs. AA + AC), P: 0.001, OR: 2.829: 95% CI: 1.543–5.185 and dominant model (AC + CC vs. AA) P: < 001, OR: 2.331, 95% CI: 1.564–3.474 the genotypes distribution increased the individual risk, plus its alleles distribution (P: < 0.001, OR: 2.004, 95% CI: 1.505–2.669). Considering SNP rs7922269 mutation significantly increased pulmonary tuberculosis risk as was observed in the homozygous GG vs. TT (P: 0.003, OR: 3.162, 95% CI: 1.431–6.989); heterozygous GT vs. TT (P: < 0.001, OR: 1.2.259, 95% CI: 1.503–3.394); dominant model (GT + GG vs. TT; P: < 0.001, OR: 2.061, 95% CI: 1.402–3.032) and the allele G (P: < 0.001, OR: 1.829, 95% CI:1.361–2.458), however no significant association was observed in the Recessive model (GG vs. TT + GT; P: 0.057, OR: 2.568, 95% CI: 0.965–4.432).ConclusionThe findings of our study strengthen the hypothesis that LIPA rs1051338 and rs7922269 polymorphism associated with increased risk for pulmonary Tb in a sample of northern Chinese population.     

Brief Report: Single‐nucleotide polymorphisms in VKORC1 are risk factors for systemic lupus erythematosus in Asians

Objective

The increased risk of thrombosis in systemic lupus erythematosus (SLE) may be partially explained by interrelated genetic pathways for thrombosis and SLE. The present study was undertaken to investigate whether 33 established and novel single‐nucleotide polymorphisms (SNPs) in 20 genes involved in hemostasis pathways that have been associated with deep venous thrombosis (DVT) in the general population are risk factors for SLE among Asian subjects.

Methods

Patients in the discovery cohort were enrolled in 1 of 2 North American SLE cohorts. Patients in the replication cohort were enrolled in 1 of 4 Asian or 2 North American cohorts. We first genotyped 263 Asian patients with SLE and 357 healthy Asian control subjects for 33 SNPs in the discovery phase, and then genotyped 5 SNPs in up to an additional 1,496 patients and 993 controls in the replication phase. Patients were compared to controls for bivariate association with minor alleles. Principal components analysis was used to control for intra‐Asian ancestry in the replication cohort.

Results

Two genetic variants in the gene VKORC1 were highly significant in both the discovery and replication cohorts: rs9934438 (in the discovery cohort, odds ratio [OR] 2.45, P = 2 × 10⁻⁹; in the replication cohort, OR 1.54, P = 4 × 10⁻⁶) and rs9923231 (in the discovery cohort, OR 2.40, P = 6 × 10⁻⁹; in the replication cohort, OR 1.53, P = 5 × 10⁻⁶). These associations were significant in the replication cohort after adjustment for intra‐Asian ancestry: for rs9934438, OR 1.34, P = 0.0029; for rs9923231, OR 1.34, P = 0.0032.

Conclusion

Genetic variants in VKORC1, which are involved in vitamin K reduction and associated with DVT, correlate with SLE development in Asian subjects. These results suggest that there may be intersecting genetic pathways for the development of SLE and thrombosis.

     

Association of carotid atherosclerosis with genetic polymorphisms of the klotho gene in patients with hypertension

Aim: Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima‐media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis. Methods: All subjects were Japanese. Eight‐hundred and fifty‐three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check‐ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks. Results: Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensive patients clearly had more atherosclerosis risk factors. Conclusion: Only in hypertensive patients was klotho rs650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension. Geriatr Gerontol Int 2010 ; 10: 311–318.     

Cytotoxic T-lymphocyte associated antigen-4 gene polymorphisms and primary biliary cirrhosis: a systematic review

Background and Aim: The cytotoxic T‐lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed on activated and regulatory T lymphocytes. Polymorphisms could have remarkable effects on susceptibility to autoimmunity. However, the associations between CTLA‐4 polymorphisms and primary biliary cirrhosis (PBC) remain ambiguous. The aim of this meta‐analysis is to determine more precise estimations of the relationship. Methods: From literature retrieval from PubMed, Web of Science, Science Direct, and the Chinese National Knowledge Infrastructure (CNKI) Database, the publications on the associations between rs231775, rs3087243, rs5742909, rs231725 and rs11571317 polymorphisms of CTLA4 and PBC through June 2011 were collected. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in fixed or random model, I² was calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects with Revman 5.1 and Stata 11. Results: Overall, a significantly increased risk was found for G versus A allele for rs231775 (OR = 1.28, 95% CI = 1.17–1.41). For rs3087243, a significant association was found for AA versus GG genotype (OR = 0.66; 95% CI = 0.55–0.80). When subgroup analysis by ethnicity was performed, the same association was only found in Caucasians. For rs231725, the OR values (95% CI) for GG versus AA, GA versus AA and G versus A allele were 0.52 (0.40–0.68), 0.74 (0.60–0.92) and 0.73 (0.61–0.88). No significant associations were found for other polymorphisms. Conclusion: The G allele of rs231775 is a risk factor for PBC, while AA genotype of rs3087243 and GG, GA and G allele of rs231725 show negative associations with PBC.     

Toll-like receptor polymorphisms and rheumatoid arthritis: a systematic review

The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and influence the clinical characteristics of RA. The authors conducted a systematic review on associations between TLR polymorphisms and RA susceptibility and clinical findings. Meta-analysis was performed if at least three comparisons of an issue were available. A total of 14 studies were included in this systematic review, which included European and Asian studies. Meta-analysis of five European studies showed no association between the TLR4 Asp299Gly (rs4986790) polymorphism and RA (OR for the minor allele = 0.907, 95 % CI = 0.755–1.088, p = 0.291). Furthermore, none of these studies found any association between the polymorphism and clinical characteristics. A significant difference between TLR9 rs187084 allele frequencies in RA patients and controls was found in one Turkish study (p = 0.003), and a moderate association between RF positivity and TLR8 rs5741883 was found in an European study (p = 0.001). The numbers of guanine–thymine [(GT)_n] repeats in intron II of the TLR2 gene were found a significantly higher S-allele frequency in Korean patients with RA than in controls (30.3 vs. 23.0 %, p = 0.03). This meta-analysis shows lack of an association between the TLR4 Asp299Gly polymorphism and RA. However, our finding suggests the possibility that TLR polymorphisms are associated with the development and clinical characteristics of RA. Because of a paucity of data of the TLR polymorphisms, case–control studies are required to determine whether TLR2, 4, 8, 9 polymorphisms contribute to RA susceptibility or severity in more than 2,000 patients and controls.     

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis

Abstract

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case–control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) ?1722T/C, CTLA-4 ?318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36–0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39–0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66–0.83; T vs. G: OR 0.72, 95% CI 0.66–0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.     

The investigation of toll-like receptor 3, 9 and 10 gene polymorphisms in Turkish rheumatoid arthritis patients

Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLRs have been reported to be associated with a range of immune-related diseases. This study was conducted to investigate the frequencies of TLR3 rs3775290, TLR9 rs187084, and TLR10 rs4129009 polymorphisms and to detect between polymorphisms and autoantibody positive as RF, collagen type II, anti-RNP, and anti-CCP in patient group. We performed a case–control study of 100 rheumatoid arthritis (RA) cases and 100 healthy controls matched on age, sex, and residence. All polymorphisms in TLRs were determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum autoantibody level was measured using quantitative ELISA. SNPs were genotyped in all samples. Our results showed that TT genotype for SNP 1237 T/C increased the RA risk significantly (p < 0.05). No statistically significant differences were found in the TLR3 and TLR10 genotypes or allele distribution between RA patients and control individuals. No associations were noted with autoantibody production and TLR3, TLR9, and TLR10 polymorphisms genotypes (p > 0.05). Our study suggests that a single nucleotide polymorphism (rs187084) in TLR9 gene may be a susceptibility factor for RA in Turkish population. Further studies are required to explore the role of TLRs gene polymorphisms in the risk of RA, especially in ethnically different populations to confirm our results.     

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG?+?GG: OR 0.48, 95% CI 0.39-0.59; TT?+?TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.